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  • 1
    Publication Date: 2018-04-03
    Description: Because the receptor tyrosine kinase c-Met plays a critical role in tumor growth, metastasis, tumor angiogenesis, and drug resistance, the c-Met axis represents an attractive therapeutic target. Herein, we report the first preclinical characterization of SCC244, a novel, potent, and highly selective inhibitor of c-Met kinase. SCC244 showed subnanomolar potency against c-Met kinase activity and high selectivity versus 312 other tested protein kinases, making it one of the most selective c-Met inhibitors described to date. Moreover, this inhibitor profoundly and specifically inhibits c-Met signal transduction and thereby suppresses the c-Met–dependent neoplastic phenotype of tumor and endothelial cells. In xenografts of human tumor cell lines or non–small cell lung cancer and hepatocellular carcinoma patient-derived tumor tissue driven by MET aberration, SCC244 administration exhibits robust antitumor activity at the well-tolerated doses. In addition, the in vivo antitumor activity of SCC244 involves the inhibition of c-Met downstream signaling via a mechanism of combined antiproliferation and antiangiogenic effects. The results of the current study provide a strong foundation for the clinical investigation of SCC244 in patients with tumors harboring c-Met pathway alterations. Mol Cancer Ther; 17(4); 751–62. ©2017 AACR .
    Print ISSN: 1535-7163
    Electronic ISSN: 1538-8514
    Topics: Medicine
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Immunological reviews 121 (1991), S. 0 
    ISSN: 1600-065X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2013-04-16
    Description: ATP-binding cassette (ABC) transporters, composed of importers and exporters, form one of the biggest protein superfamilies that transport a variety of substrates across the membrane, powered by ATP hydrolysis. Most ABC transporters are composed of two transmembrane domains and two cytoplasmic nucleotide-binding domains. Also, importers from prokaryotes usually have extra solute-binding proteins in the periplasm that are responsible for the binding of substrates. Structures of importers have been reported that suggested a two-state model for the transport mechanism. Energy-coupling factor (ECF) transporters belong to a new class of ATP-binding cassette importers. Each ECF transporter comprises an energy-coupling module consisting of a transmembrane T protein (EcfT), two nucleotide-binding proteins (EcfA and EcfA'), and another transmembrane substrate-specific binding S protein (EcfS). Despite the similarities with ABC transporters, ECF transporters have different organizational and functional properties. The lack of solute-binding proteins in ECF transporters differentiates them clearly from the canonical ABC importers. Previously reported structures of the EcfS proteins RibU and ThiT clearly demonstrated the binding site of substrate riboflavin and thiamine, respectively. However, the organization of the four different components and the transport mechanism of ECF transporters remain unknown. Here we present the structure of an intact folate ECF transporter from Lactobacillus brevis at a resolution of 3 A. This structure was captured in an inward-facing, nucleotide-free conformation with no bound substrate. The folate-binding protein FolT is nearly parallel to the membrane and is bound almost entirely by EcfT, which adopts an L shape and connects to EcfA and EcfA' through two coupling helices. Two conserved XRX motifs from the coupling helices of EcfT have a vital role in energy coupling by docking into EcfA-EcfA'. We propose a transport model that involves a substantial conformational change of FolT.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Ke -- Zhang, Minhua -- Zhao, Qin -- Yu, Fang -- Guo, Hui -- Wang, Chengyuan -- He, Fangyuan -- Ding, Jianping -- Zhang, Peng -- England -- Nature. 2013 May 9;497(7448):268-71. doi: 10.1038/nature12046. Epub 2013 Apr 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Key Laboratory of Plant Molecular Genetics, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 300 Fenglin Road, Shanghai 200032, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23584589" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/chemistry ; Adenosine Triphosphatases/metabolism ; Adenosine Triphosphate/metabolism ; Amino Acid Motifs ; Bacterial Proteins/*chemistry/metabolism ; Conserved Sequence ; Crystallography, X-Ray ; Folic Acid Transporters/*chemistry/metabolism ; Lactobacillus brevis/*chemistry ; Models, Molecular ; Protein Conformation ; Protein Subunits/chemistry/metabolism ; Proteolipids/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-04-18
    Description: Reactive oxygen species (ROS) produced by phagocytes are essential for host defence against bacterial and fungal infections. Individuals with defective ROS production machinery develop chronic granulomatous disease. Conversely, excessive ROS can cause collateral tissue damage during inflammatory processes and therefore needs to be tightly regulated. Here we describe a protein, we termed negative regulator of ROS (NRROS), which limits ROS generation by phagocytes during inflammatory responses. NRROS expression in phagocytes can be repressed by inflammatory signals. NRROS-deficient phagocytes produce increased ROS upon inflammatory challenges, and mice lacking NRROS in their phagocytes show enhanced bactericidal activity against Escherichia coli and Listeria monocytogenes. Conversely, these mice develop severe experimental autoimmune encephalomyelitis owing to oxidative tissue damage in the central nervous system. Mechanistically, NRROS is localized to the endoplasmic reticulum, where it directly interacts with nascent NOX2 (also known as gp91(phox) and encoded by Cybb) monomer, one of the membrane-bound subunits of the NADPH oxidase complex, and facilitates the degradation of NOX2 through the endoplasmic-reticulum-associated degradation pathway. Thus, NRROS provides a hitherto undefined mechanism for regulating ROS production--one that enables phagocytes to produce higher amounts of ROS, if required to control invading pathogens, while minimizing unwanted collateral tissue damage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Noubade, Rajkumar -- Wong, Kit -- Ota, Naruhisa -- Rutz, Sascha -- Eidenschenk, Celine -- Valdez, Patricia A -- Ding, Jiabing -- Peng, Ivan -- Sebrell, Andrew -- Caplazi, Patrick -- DeVoss, Jason -- Soriano, Robert H -- Sai, Tao -- Lu, Rongze -- Modrusan, Zora -- Hackney, Jason -- Ouyang, Wenjun -- England -- Nature. 2014 May 8;509(7499):235-9. doi: 10.1038/nature13152. Epub 2014 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA [2] Flexus Biosciences, 75 Shoreway Road, Suite D, San Carlos, California 94070, USA (R.N.); American Society for Biochemistry and Molecular Biology, 11200 Rockville Pike, Suite 302, Rockville, Maryland 20852, USA (P.A.V.). ; Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Antibody Engineering, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Pathology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Bioinformatics, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739962" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autoimmunity/genetics ; Bone Marrow Cells/cytology ; Central Nervous System/metabolism/pathology ; Encephalomyelitis, Autoimmune, Experimental/*immunology/*metabolism/pathology ; Endoplasmic Reticulum/enzymology/metabolism ; Escherichia coli/*immunology ; Female ; Inflammation/immunology/metabolism/pathology ; Listeria monocytogenes/*immunology ; Macrophages/cytology/enzymology/immunology/metabolism ; Male ; Mice ; NADPH Oxidase/metabolism ; Oxidation-Reduction ; Oxidative Stress ; Phagocytes/cytology/immunology/metabolism ; Proteins/genetics/*metabolism ; Reactive Oxygen Species/*antagonists & inhibitors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2014-07-22
    Description: Plant resistance (R) genes are a crucial component in plant defence against pathogens. Although R genes often fail to provide durable resistance in an agricultural context, they frequently persist as long-lived balanced polymorphisms in nature. Standard theory explains the maintenance of such polymorphisms through a balance of the costs and benefits of resistance and virulence in a tightly coevolving host-pathogen pair. However, many plant-pathogen interactions lack such specificity. Whether, and how, balanced polymorphisms are maintained in diffusely interacting species is unknown. Here we identify a naturally interacting R gene and effector pair in Arabidopsis thaliana and its facultative plant pathogen, Pseudomonas syringae. The protein encoded by the R gene RPS5 recognizes an AvrPphB homologue (AvrPphB2) and exhibits a balanced polymorphism that has been maintained for over 2 million years (ref. 3). Consistent with the presence of an ancient balanced polymorphism, the R gene confers a benefit when plants are infected with P. syringae carrying avrPphB2 but also incurs a large cost in the absence of infection. RPS5 alleles are maintained at intermediate frequencies in populations globally, suggesting ubiquitous selection for resistance. However, the presence of P. syringae carrying avrPphB is probably insufficient to explain the RPS5 polymorphism. First, avrPphB homologues occur at very low frequencies in P. syringae populations on A. thaliana. Second, AvrPphB only rarely confers a virulence benefit to P. syringae on A. thaliana. Instead, we find evidence that selection for RPS5 involves multiple non-homologous effectors and multiple pathogen species. These results and an associated model suggest that the R gene polymorphism in A. thaliana may not be maintained through a tightly coupled interaction involving a single coevolved R gene and effector pair. More likely, the stable polymorphism is maintained through complex and diffuse community-wide interactions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696508/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696508/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karasov, Talia L -- Kniskern, Joel M -- Gao, Liping -- DeYoung, Brody J -- Ding, Jing -- Dubiella, Ullrich -- Lastra, Ruben O -- Nallu, Sumitha -- Roux, Fabrice -- Innes, Roger W -- Barrett, Luke G -- Hudson, Richard R -- Bergelson, Joy -- R01 GM046451/GM/NIGMS NIH HHS/ -- R01 GM057994/GM/NIGMS NIH HHS/ -- R01 GM062504/GM/NIGMS NIH HHS/ -- R01 GM083068/GM/NIGMS NIH HHS/ -- R01GM046451/GM/NIGMS NIH HHS/ -- T32 GM007197/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Aug 28;512(7515):436-40. doi: 10.1038/nature13439. Epub 2014 Jul 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637, USA [2] Committee on Genetics Genomics and Systems Biology, University of Chicago, Chicago, Illinois 60637, USA [3]. ; 1] Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637, USA [2] Monsanto Vegetable Seeds, 37437 State Highway 16, Woodland, California 95695, USA (J.M.K.); State Key Laboratory of Plant Genetics and Germplasm Enhancement and College of Horticulture, Nanjing Agricultural University, Nanjing, China (J.D.); CSIRO Plant Industry, GPO Box 1600, Canberra, ACT 2601, Australia (L.G.B.). [3]. ; Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637, USA. ; Department of Biology, Indiana University, Bloomington, Indiana 47405, USA. ; 1] Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637, USA [2] Monsanto Vegetable Seeds, 37437 State Highway 16, Woodland, California 95695, USA (J.M.K.); State Key Laboratory of Plant Genetics and Germplasm Enhancement and College of Horticulture, Nanjing Agricultural University, Nanjing, China (J.D.); CSIRO Plant Industry, GPO Box 1600, Canberra, ACT 2601, Australia (L.G.B.). ; 1] INRA, Laboratoire des Interactions Plantes-Microorganismes (LIPM), UMR441, F-31326 Castanet-Tolosan, France [2] CNRS, Laboratoire des Interactions Plantes-Microorganismes (LIPM), UMR2594, F-31326 Castanet-Tolosan, France [3] Laboratoire Genetique et Evolution des Populations Vegetales, UMR CNRS 8198, Universite des Sciences et Technologies de Lille - Lille 1, F-59655 Villeneuve d'Ascq Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043057" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Arabidopsis/*genetics/*microbiology ; Arabidopsis Proteins/*genetics/metabolism ; Bacterial Proteins/genetics/metabolism ; *Evolution, Molecular ; Genes, Plant/genetics ; Host-Pathogen Interactions/*genetics ; Models, Genetic ; Plant Immunity/genetics ; *Polymorphism, Genetic ; Pseudomonas syringae/*genetics/pathogenicity ; Selection, Genetic/*genetics ; Virulence/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2015-01-28
    Description: The origin of mutations is central to understanding evolution and of key relevance to health. Variation occurs non-randomly across the genome, and mechanisms for this remain to be defined. Here we report that the 5' ends of Okazaki fragments have significantly increased levels of nucleotide substitution, indicating a replicative origin for such mutations. Using a novel method, emRiboSeq, we map the genome-wide contribution of polymerases, and show that despite Okazaki fragment processing, DNA synthesized by error-prone polymerase-alpha (Pol-alpha) is retained in vivo, comprising approximately 1.5% of the mature genome. We propose that DNA-binding proteins that rapidly re-associate post-replication act as partial barriers to Pol-delta-mediated displacement of Pol-alpha-synthesized DNA, resulting in incorporation of such Pol-alpha tracts and increased mutation rates at specific sites. We observe a mutational cost to chromatin and regulatory protein binding, resulting in mutation hotspots at regulatory elements, with signatures of this process detectable in both yeast and humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374164/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374164/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reijns, Martin A M -- Kemp, Harriet -- Ding, James -- de Proce, Sophie Marion -- Jackson, Andrew P -- Taylor, Martin S -- MC_PC_U127580972/Medical Research Council/United Kingdom -- MC_PC_U127597124/Medical Research Council/United Kingdom -- MC_U127597124/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2015 Feb 26;518(7540):502-6. doi: 10.1038/nature14183. Epub 2015 Jan 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical and Developmental Genetics, MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Biomedical Systems Analysis, MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25624100" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Chromatin/chemistry/metabolism ; Conserved Sequence/genetics ; DNA/*biosynthesis/*genetics ; DNA Polymerase I/metabolism ; DNA Polymerase III/metabolism ; DNA Replication/*genetics ; DNA-Binding Proteins/metabolism ; Evolution, Molecular ; Genome, Human/*genetics ; Humans ; Models, Biological ; Mutagenesis/genetics ; Mutation/*genetics ; Protein Binding ; Saccharomyces cerevisiae/genetics ; Transcription Factors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2016-05-27
    Description: Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okbay, Aysu -- Beauchamp, Jonathan P -- Fontana, Mark Alan -- Lee, James J -- Pers, Tune H -- Rietveld, Cornelius A -- Turley, Patrick -- Chen, Guo-Bo -- Emilsson, Valur -- Meddens, S Fleur W -- Oskarsson, Sven -- Pickrell, Joseph K -- Thom, Kevin -- Timshel, Pascal -- de Vlaming, Ronald -- Abdellaoui, Abdel -- Ahluwalia, Tarunveer S -- Bacelis, Jonas -- Baumbach, Clemens -- Bjornsdottir, Gyda -- Brandsma, Johannes H -- Pina Concas, Maria -- Derringer, Jaime -- Furlotte, Nicholas A -- Galesloot, Tessel E -- Girotto, Giorgia -- Gupta, Richa -- Hall, Leanne M -- Harris, Sarah E -- Hofer, Edith -- Horikoshi, Momoko -- Huffman, Jennifer E -- Kaasik, Kadri -- Kalafati, Ioanna P -- Karlsson, Robert -- Kong, Augustine -- Lahti, Jari -- van der Lee, Sven J -- deLeeuw, Christiaan -- Lind, Penelope A -- Lindgren, Karl-Oskar -- Liu, Tian -- Mangino, Massimo -- Marten, Jonathan -- Mihailov, Evelin -- Miller, Michael B -- van der Most, Peter J -- Oldmeadow, Christopher -- Payton, Antony -- Pervjakova, Natalia -- Peyrot, Wouter J -- Qian, Yong -- Raitakari, Olli -- Rueedi, Rico -- Salvi, Erika -- Schmidt, Borge -- Schraut, Katharina E -- Shi, Jianxin -- Smith, Albert V -- Poot, Raymond A -- St Pourcain, Beate -- Teumer, Alexander -- Thorleifsson, Gudmar -- Verweij, Niek -- Vuckovic, Dragana -- Wellmann, Juergen -- Westra, Harm-Jan -- Yang, Jingyun -- Zhao, Wei -- Zhu, Zhihong -- Alizadeh, Behrooz Z -- Amin, Najaf -- Bakshi, Andrew -- Baumeister, Sebastian E -- Biino, Ginevra -- Bonnelykke, Klaus -- Boyle, Patricia A -- Campbell, Harry -- Cappuccio, Francesco P -- Davies, Gail -- De Neve, Jan-Emmanuel -- Deloukas, Panos -- Demuth, Ilja -- Ding, Jun -- Eibich, Peter -- Eisele, Lewin -- Eklund, Niina -- Evans, David M -- Faul, Jessica D -- Feitosa, Mary F -- Forstner, Andreas J -- Gandin, Ilaria -- Gunnarsson, Bjarni -- Halldorsson, Bjarni V -- Harris, Tamara B -- Heath, Andrew C -- Hocking, Lynne J -- Holliday, Elizabeth G -- Homuth, Georg -- Horan, Michael A -- Hottenga, Jouke-Jan -- de Jager, Philip L -- Joshi, Peter K -- Jugessur, Astanand -- Kaakinen, Marika A -- Kahonen, Mika -- Kanoni, Stavroula -- Keltigangas-Jarvinen, Liisa -- Kiemeney, Lambertus A L M -- Kolcic, Ivana -- Koskinen, Seppo -- Kraja, Aldi T -- Kroh, Martin -- Kutalik, Zoltan -- Latvala, Antti -- Launer, Lenore J -- Lebreton, Mael P -- Levinson, Douglas F -- Lichtenstein, Paul -- Lichtner, Peter -- Liewald, David C M -- LifeLines Cohort Study -- Loukola, Anu -- Madden, Pamela A -- Magi, Reedik -- Maki-Opas, Tomi -- Marioni, Riccardo E -- Marques-Vidal, Pedro -- Meddens, Gerardus A -- McMahon, George -- Meisinger, Christa -- Meitinger, Thomas -- Milaneschi, Yusplitri -- Milani, Lili -- Montgomery, Grant W -- Myhre, Ronny -- Nelson, Christopher P -- Nyholt, Dale R -- Ollier, William E R -- Palotie, Aarno -- Paternoster, Lavinia -- Pedersen, Nancy L -- Petrovic, Katja E -- Porteous, David J -- Raikkonen, Katri -- Ring, Susan M -- Robino, Antonietta -- Rostapshova, Olga -- Rudan, Igor -- Rustichini, Aldo -- Salomaa, Veikko -- Sanders, Alan R -- Sarin, Antti-Pekka -- Schmidt, Helena -- Scott, Rodney J -- Smith, Blair H -- Smith, Jennifer A -- Staessen, Jan A -- Steinhagen-Thiessen, Elisabeth -- Strauch, Konstantin -- Terracciano, Antonio -- Tobin, Martin D -- Ulivi, Sheila -- Vaccargiu, Simona -- Quaye, Lydia -- van Rooij, Frank J A -- Venturini, Cristina -- Vinkhuyzen, Anna A E -- Volker, Uwe -- Volzke, Henry -- Vonk, Judith M -- Vozzi, Diego -- Waage, Johannes -- Ware, Erin B -- Willemsen, Gonneke -- Attia, John R -- Bennett, David A -- Berger, Klaus -- Bertram, Lars -- Bisgaard, Hans -- Boomsma, Dorret I -- Borecki, Ingrid B -- Bultmann, Ute -- Chabris, Christopher F -- Cucca, Francesco -- Cusi, Daniele -- Deary, Ian J -- Dedoussis, George V -- van Duijn, Cornelia M -- Eriksson, Johan G -- Franke, Barbara -- Franke, Lude -- Gasparini, Paolo -- Gejman, Pablo V -- Gieger, Christian -- Grabe, Hans-Jorgen -- Gratten, Jacob -- Groenen, Patrick J F -- Gudnason, Vilmundur -- van der Harst, Pim -- Hayward, Caroline -- Hinds, David A -- Hoffmann, Wolfgang -- Hypponen, Elina -- Iacono, William G -- Jacobsson, Bo -- Jarvelin, Marjo-Riitta -- Jockel, Karl-Heinz -- Kaprio, Jaakko -- Kardia, Sharon L R -- Lehtimaki, Terho -- Lehrer, Steven F -- Magnusson, Patrik K E -- Martin, Nicholas G -- McGue, Matt -- Metspalu, Andres -- Pendleton, Neil -- Penninx, Brenda W J H -- Perola, Markus -- Pirastu, Nicola -- Pirastu, Mario -- Polasek, Ozren -- Posthuma, Danielle -- Power, Christine -- Province, Michael A -- Samani, Nilesh J -- Schlessinger, David -- Schmidt, Reinhold -- Sorensen, Thorkild I A -- Spector, Tim D -- Stefansson, Kari -- Thorsteinsdottir, Unnur -- Thurik, A Roy -- Timpson, Nicholas J -- Tiemeier, Henning -- Tung, Joyce Y -- Uitterlinden, Andre G -- Vitart, Veronique -- Vollenweider, Peter -- Weir, David R -- Wilson, James F -- Wright, Alan F -- Conley, Dalton C -- Krueger, Robert F -- Davey Smith, George -- Hofman, Albert -- Laibson, David I -- Medland, Sarah E -- Meyer, Michelle N -- Yang, Jian -- Johannesson, Magnus -- Visscher, Peter M -- Esko, Tonu -- Koellinger, Philipp D -- Cesarini, David -- Benjamin, Daniel J -- P01-AG005842/AG/NIA NIH HHS/ -- P01-AG005842-20S2/AG/NIA NIH HHS/ -- P30-AG012810/AG/NIA NIH HHS/ -- R01-AG042568/AG/NIA NIH HHS/ -- T32-AG000186-23/AG/NIA NIH HHS/ -- England -- Nature. 2016 May 11;533(7604):539-42. doi: 10.1038/nature17671.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, 3062 PA, The Netherlands. ; Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands. ; Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, 3062 PA, The Netherlands. ; Department of Economics, Harvard University, Cambridge, Massachusetts 02138, USA. ; Center for Economic and Social Research, University of Southern California, Los Angeles, California 90089-3332, USA. ; Department of Psychology, University of Minnesota Twin Cities, Minneapolis, Minnesota 55455, USA. ; Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 2116, USA. ; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen 2100, Denmark. ; Statens Serum Institut, Department of Epidemiology Research, Copenhagen 2300, Denmark. ; Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia. ; Icelandic Heart Association, Kopavogur 201, Iceland. ; Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik 107, Iceland. ; Department of Complex Trait Genetics, VU University, Center for Neurogenomics and Cognitive Research, Amsterdam, 1081 HV, The Netherlands. ; Amsterdam Business School, University of Amsterdam, Amsterdam, 1018 TV, The Netherlands. ; Department of Government, Uppsala University, Uppsala 751 20, Sweden. ; New York Genome Center, New York, New York 10013, USA. ; Department of Economics, New York University, New York, New York 10012, USA. ; Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark Lyngby 2800, Denmark. ; Department of Biological Psychology, VU University Amsterdam, Amsterdam, 1081 BT, The Netherlands. ; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen 2820, Denmark. ; Steno Diabetes Center, Gentofte 2820, Denmark. ; Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg 416 85, Sweden. ; Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg 85764, Germany. ; Institute of Epidemiology II, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg 85764, Germany. ; deCODE Genetics/Amgen Inc., Reykjavik 101, Iceland. ; Department of Cell Biology, Erasmus Medical Center Rotterdam, 3015 CN, The Netherlands. ; Istituto di Ricerca Genetica e Biomedica U.O.S. di Sassari, National Research Council of Italy, Sassari 07100, Italy. ; Psychology, University of Illinois, Champaign, Illinois 61820, USA. ; 23andMe, Inc., Mountain View, California 94041, USA. ; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, 6500 HB, The Netherlands. ; Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34100, Italy. ; Department of Public Health, University of Helsinki, 00014 Helsinki, Finland. ; Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK. ; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK. ; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK. ; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Department of Neurology, General Hospital and Medical University Graz, Graz 8036, Austria. ; Institute for Medical Informatics, Statistics and Documentation, General Hospital and Medical University Graz, Graz 8036, Austria. ; Oxford Centre for Diabetes, Endocrinology &Metabolism, University of Oxford, Oxford OX3 7LE, UK. ; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. ; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Institute of Behavioural Sciences, University of Helsinki, 00014 Helsinki, Finland. ; Nutrition and Dietetics, Health Science and Education, Harokopio University, Athens 17671, Greece. ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden. ; Folkhalsan Research Centre, 00014 Helsingfors, Finland. ; Institute for Computing and Information Sciences, Radboud University Nijmegen, Nijmegen, 6525 EC, The Netherlands. ; Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia. ; Lifespan Psychology, Max Planck Institute for Human Development, Berlin 14195, Germany. ; Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. ; NIHR Biomedical Research Centre, Guy's and St. Thomas' Foundation Trust, London SE1 7EH, UK. ; Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. ; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands. ; Public Health Stream, Hunter Medical Research Institute, New Lambton, NSW 2305, Australia. ; Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW 2300, Australia. ; Centre for Integrated Genomic Medical Research, Institute of Population Health, The University of Manchester, Manchester M13 9PT, UK. ; Human Communication and Deafness, School of Psychological Sciences, The University of Manchester, Manchester M13 9PL, UK. ; Department of Health, THL-National Institute for Health and Welfare, 00271 Helsinki, Finland. ; Psychiatry, VU University Medical Center &GGZ inGeest, Amsterdam, 1081 HL, The Netherlands. ; Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland 21224, USA. ; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20521 Turku, Finland. ; Department of Medical Genetics, University of Lausanne, Lausanne 1005, Switzerland. ; Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland. ; Department Of Health Sciences, University of Milan, Milano 20142, Italy. ; Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen 45147, Germany. ; Centre for Global Health Research, The Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-9780, USA. ; Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland. ; MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK. ; School of Oral and Dental Sciences, University of Bristol, Bristol BS1 2LY, UK. ; Institute for Community Medicine, University Medicine Greifswald, Greifswald 17475, Germany. ; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB, The Netherlands. ; Institute of Epidemiology and Social Medicine, University of Munster, Munster 48149, Germany. ; Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Partners Center for Personalized Genetic Medicine, Boston, Massachusetts 02115, USA. ; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois 60612, USA. ; Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA. ; Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands. ; Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg D-93053, Germany. ; Institute of Molecular Genetics, National Research Council of Italy, Pavia 27100, Italy. ; Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA. ; Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK. ; Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. ; Said Business School, University of Oxford, Oxford OX1 1HP, UK. ; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. ; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah 21589, Saudi Arabia. ; The Berlin Aging Study II; Research Group on Geriatrics, Charite - Universitatsmedizin Berlin, Germany, Berlin 13347, Germany. ; Institute of Medical and Human Genetics, Charite-Universitatsmedizin, Berlin, Berlin 13353, Germany. ; German Socio- Economic Panel Study, DIW Berlin, Berlin 10117, Germany. ; Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK. ; The University of Queensland Diamantina Institute, The Translational Research Institute, Brisbane, QLD 4102, Australia. ; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri 63018, USA. ; Institute of Human Genetics, University of Bonn, Bonn 53127, Germany. ; Department of Genomics, Life and Brain Center, University of Bonn, Bonn 53127, Germany. ; Institute of Biomedical and Neural Engineering, School of Science and Engineering, Reykjavik University, Reykjavik 101, Iceland. ; Laboratory of Epidemiology, Demography, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892-9205, USA. ; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. ; Division of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK. ; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17475, Germany. ; Manchester Medical School, The University of Manchester, Manchester M13 9PT, UK. ; Program in Translational NeuroPsychiatric Genomics, Departments of Neurology &Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. ; Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Genes and Environment, Norwegian Institute of Public Health, N-0403 Oslo, Norway. ; Department of Genomics of Common Disease, Imperial College London, London, W12 0NN, UK. ; Department of Clinical Physiology, Tampere University Hospital, 33521 Tampere, Finland. ; Department of Clinical Physiology, University of Tampere, School of Medicine, 33014 Tampere, Finland. ; Public Health, Medical School, University of Split, 21000 Split, Croatia. ; Institute of Social and Preventive Medicine, Lausanne University Hospital (CHUV), Lausanne 1010, Switzerland. ; Neuroepidemiology Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892-9205, USA. ; Amsterdam Brain and Cognition Center, University of Amsterdam, Amsterdam, 1018 XA, The Netherlands. ; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305-5797, USA. ; Institute of Human Genetics, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg 85764, Germany. ; Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK. ; Department of Internal Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne 1011, Switzerland. ; Tema BV, Hoofddorp, 2131 HE, The Netherlands. ; Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia. ; Institute of Health and Biomedical Innovation, Queensland Institute of Technology, Brisbane, QLD 4059, Australia. ; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; Psychiatric &Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland. ; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Medical Genetics, Institute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste 34100, Italy. ; Social Impact, Arlington, Virginia 22201, USA. ; Department of Economics, University of Minnesota Twin Cities, Minneapolis, Minnesota 55455, USA. ; Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston, Illinois 60201-3137, USA. ; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois 60637, USA. ; Public Health Genomics Unit, National Institute for Health and Welfare, 00300 Helsinki, Finland. ; Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, General Hospital and Medical University, Graz, Graz 8010, Austria. ; Information Based Medicine Stream, Hunter Medical Research Institute, New Lambton, NSW 2305, Australia. ; Medical Research Institute, University of Dundee, Dundee DD1 9SY, UK. ; Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Science, University of Leuven, Leuven 3000, Belgium. ; R&D VitaK Group, Maastricht University, Maastricht, 6229 EV, The Netherlands. ; Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg 85764, Germany. ; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig Maximilians-Universitat, Munich 81377, Germany. ; Department of Geriatrics, Florida State University College of Medicine, Tallahassee, Florida 32306, USA. ; Department of Health Sciences and Genetics, University of Leicester, Leicester LE1 7RH, UK. ; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands. ; Research Center for Group Dynamics, Institute for Social Research, University of Michigan, Ann Arbor, Michigan 48104, USA. ; Platform for Genome Analytics, Institutes of Neurogenetics &Integrative and Experimental Genomics, University of Lubeck, Lubeck 23562, Germany. ; Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK. ; Department of Health Sciences, Community &Occupational Medicine, University of Groningen, University Medical Center Groningen, Groningen, 9713 AV, The Netherlands. ; Department of Psychology, Union College, Schenectady, New York 12308, USA. ; Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari 9042, Italy. ; Institute of Biomedical Technologies, Italian National Research Council, Segrate (Milano) 20090, Italy. ; Department of General Practice and Primary Health Care, University of Helsinki, 00014 Helsinki, Finland. ; Departments of Human Genetics and Psychiatry, Donders Centre for Neuroscience, Nijmegen, 6500 HB, The Netherlands. ; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB, The Netherlands. ; Sidra, Experimental Genetics Division, Sidra, Doha 26999, Qatar. ; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald 17475, Germany. ; Department of Psychiatry and Psychotherapy, HELIOS-Hospital Stralsund, Stralsund 18437, Germany. ; Econometric Institute, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, 3062 PA, The Netherlands. ; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, 1105 AZ, The Netherlands. ; Generation Scotland, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Centre for Population Health Research, School of Health Sciences and Sansom Institute, University of South Australia, Adelaide, SA 5000, Australia. ; South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia. ; Population, Policy and Practice, UCL Institute of Child Health, London WC1N 1EH, UK. ; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment &Health, School of Public Health, Imperial College London, London W2 1PG, UK. ; Center for Life Course Epidemiology, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland. ; Unit of Primary Care, Oulu University Hospital, 90029 Oulu, Finland. ; Biocenter Oulu, University of Oulu, 90014 Oulu, Finland. ; Fimlab Laboratories, 33520 Tampere, Finland. ; Department of Clinical Chemistry, University of Tampere, School of Medicine, 33014 Tampere, Finland. ; Economics, NYU Shanghai, 200122 Pudong, China. ; Policy Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada. ; Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia. ; Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia. ; Centre for Clinical and Cognitive Neuroscience, Institute Brain Behaviour and Mental Health, Salford Royal Hospital, Manchester M6 8HD, UK. ; Manchester Institute for Collaborative Research in Ageing, University of Manchester, Manchester M13 9PL, UK. ; Faculty of Medicine, University of Split, Split 21000, Croatia. ; Department of Clinical Genetics, VU Medical Centre, Amsterdam, 1081 HV, The Netherlands. ; Institute of Preventive Medicine. Bispebjerg and Frederiksberg Hospitals, The Capital Region, Frederiksberg 2000, Denmark. ; Montpellier Business School, Montpellier 34080, France. ; Panteia, Zoetermeer, 2715 CA, The Netherlands. ; Department of Psychiatry, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands. ; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands. ; Department of Sociology, New York University, New York, New York 10012, USA. ; School of Medicine, New York University, New York, New York 10016, USA. ; Bioethics Program, Union Graduate College - Icahn School of Medicine at Mount Sinai, Schenectady, New York 12308, USA. ; Department of Economics, Stockholm School of Economics, Stockholm 113 83, Sweden. ; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Research Institute for Industrial Economics, Stockholm 10215, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27225129" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2011-08-06
    Description: The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine modifications are reversed. Here, we demonstrate that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG). Depletion of TDG in mouse embyronic stem cells leads to accumulation of 5caC to a readily detectable level. These data suggest that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462231/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462231/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Yu-Fei -- Li, Bin-Zhong -- Li, Zheng -- Liu, Peng -- Wang, Yang -- Tang, Qingyu -- Ding, Jianping -- Jia, Yingying -- Chen, Zhangcheng -- Li, Lin -- Sun, Yan -- Li, Xiuxue -- Dai, Qing -- Song, Chun-Xiao -- Zhang, Kangling -- He, Chuan -- Xu, Guo-Liang -- 1S10RR027643-01/RR/NCRR NIH HHS/ -- GM071440/GM/NIGMS NIH HHS/ -- R01 GM071440/GM/NIGMS NIH HHS/ -- S10 RR027643/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2011 Sep 2;333(6047):1303-7. doi: 10.1126/science.1210944. Epub 2011 Aug 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Group of DNA Metabolism, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21817016" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/metabolism ; Animals ; Cell Line ; Cytosine/*analogs & derivatives/metabolism ; DNA/*metabolism ; DNA Methylation ; DNA-Binding Proteins/genetics/*metabolism ; Embryonic Stem Cells ; HEK293 Cells ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Mice ; Oxidation-Reduction ; Proto-Oncogene Proteins/genetics/*metabolism ; RNA, Small Interfering ; Thymine DNA Glycosylase/genetics/*metabolism ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2018-04-20
    Description: Diamonds have substantial hardness and durability, but attempting to deform diamonds usually results in brittle fracture. We demonstrate ultralarge, fully reversible elastic deformation of nanoscale (~300 nanometers) single-crystalline and polycrystalline diamond needles. For single-crystalline diamond, the maximum tensile strains (up to 9%) approached the theoretical elastic limit, and the corresponding maximum tensile stress reached ~89 to 98 gigapascals. After combining systematic computational simulations and characterization of pre- and postdeformation structural features, we ascribe the concurrent high strength and large elastic strain to the paucity of defects in the small-volume diamond nanoneedles and to the relatively smooth surfaces compared with those of microscale and larger specimens. The discovery offers the potential for new applications through optimized design of diamond nanostructure, geometry, elastic strains, and physical properties.
    Keywords: Engineering, Materials Science
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2018-04-18
    Description: Objectives The aim of this study was to explore the prognostic value of ki67 as a marker in patients with non-muscle invasive bladder cancer (NMIBC) treated with BCG. Methods Studies were systematically retrieved from the relevant databases (Web of Science, PubMed, Cochrane Library and Embase), and the expiry date was May 2017. The research steps referred to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Results A total of 11 studies that complied with the inclusion criteria were included. The expression of ki67 was not statistically significantly associated with recurrence-free survival (RFS) (HR 1.331; 95% CI 0.980 to 1.809). No significant heterogeneity was found among all included studies ( I 2 =36.7%, p=0.148). The expression of ki67 was statistically significantly associated with progression-free survival (PFS) (HR 2.567; 95% CI 1.562 to 4.219), and the overexpression of ki67 was the risk factor for PFS. Significant heterogeneity was noted among all the included studies ( I 2 =55.6%, p=0.021). The studies that might cause heterogeneity were excluded using the Galbraith plot, and then the meta-analysis was performed again. The results showed that the expression of ki67 was still associated with PFS (HR 2.922; 95% CI 2.002 to 4.266). Conclusions The overexpression of ki67 was the risk factor for PFS, and the relationship between the expression of ki67 and RFS was not statistically significant in patients with NMIBC treated with BCG intravesical immunotherapy. Well-designed, prospective, with a large sample size are still needed to validate the findings.
    Keywords: Open access, Urology
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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